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A Study to Evaluate ALN-AGT01 in Patients With Hypertension

  • Clinicaltrials.gov identifier

    NCT03934307

  • Recruitment Status

    Recruiting

  • First Posted

    May 1, 2019

  • Last update posted

    June 15, 2021

Study Description

Brief summary:

The purpose of this study is to evaluate the safety, tolerability, pharmacokinetic (PK), and pharmacodynamic (PD) effects of subcutaneous (SC) ALN-AGT01 in participants with hypertension. The study will be conducted in 4 parts: Part A will be a single ascending dose (SAD) phase in hypertensive participants, Part B will be a single dose (SD) phase in hypertensive participants with controlled salt intake, Part D will be a MD phase in hypertensive participants who are obese, and Part E will be an open-label SD phase with co-administration of irbesartan in hypertensive patients.

  • Condition or Disease:Hypertension
  • Intervention/Treatment: Drug: ALN-AGT01
    Drug: ALN-AGT01-Matching Placebo
    Drug: Irbesartan
    Drug: Irbesartan-Matching Placebo
  • Phase: Phase 1

Detailed Description

N/A

Study Design

  • Study Type: Interventional
  • Estimated Enrollment: 160 participants
  • Allocation: Randomized
  • Intervention Model: Parallel Assignment
  • Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
  • Primary Purpose: Treatment
  • Official Title: A Phase 1, Randomized, Double-Blind, Placebo-Controlled Single Dose and Active Comparator-Controlled Multiple Dose Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of Subcutaneously Administered ALN-AGT01 in Patients With Hypertension
  • Actual Study Start Date: May 2019
  • Estimated Primary Completion Date: December 2021
  • Estimated Study Completion Date: December 2021

Arms and interventions

Arm Intervention/treatment
Experimental: Part A: SAD: ALN-AGT01
Participants will be administered a single dose of ALN-AGT01.
Drug: ALN-AGT01
ALN-AGT01 will be administered by subcutaneous (SC) injection.
Experimental: Part B: SD: ALN-AGT01
Participants with controlled salt intake will be administered a single dose of ALN-AGT01.
Drug: ALN-AGT01
ALN-AGT01 will be administered by subcutaneous (SC) injection.
Experimental: Part D: MD: ALN-AGT01 + Irbesartan-Matching Placebo
Participants, who are obese, will be administered multiple doses of ALN-AGT01 and irbesartan-matching placebo.
Drug: ALN-AGT01
ALN-AGT01 will be administered by subcutaneous (SC) injection.

Drug: Irbesartan-Matching Placebo
Irbesartan-matching placebo will be administered orally.
Experimental: Part E: Open Label: ALN-AGT01 + Irbesartan
Participants will be administered a single dose of ALN-AGT01 and multiple doses of irbesartan.
Drug: ALN-AGT01
ALN-AGT01 will be administered by subcutaneous (SC) injection.

Drug: Irbesartan
Irbesartan will be administered orally.
Placebo Comparator: Part A: SAD: ALN-AGT01-Matching Placebo
Participants will be administered a single dose of ALN-AGT01-matching placebo.
Drug: ALN-AGT01-Matching Placebo
Normal saline (0.9% NaCl) matching volume of ALN-AGT01 doses will be administered SC.
Placebo Comparator: Part B: SD: ALN-AGT01-Matching Placebo
Participants with controlled salt intake will be administered a single dose of ALN-AGT01-matching placebo.
Drug: ALN-AGT01-Matching Placebo
Normal saline (0.9% NaCl) matching volume of ALN-AGT01 doses will be administered SC.
Active Comparator: Part D: MD: ALN-AGT01-Matching Placebo + Irbesartan
Participants, who are obese, will be administered multiple doses of ALN-AGT01-matching placebo and irbesartan.
Drug: ALN-AGT01-Matching Placebo
Normal saline (0.9% NaCl) matching volume of ALN-AGT01 doses will be administered SC.

Drug: Irbesartan
Irbesartan will be administered orally.

Outcome Measures

  • Primary Outcome Measures: 1. Number of Participants with Adverse Events (AEs) [ Time Frame: Parts A, B and E: each up to approximately 12 months; Part D: up to approximately 18 months ]
  • Secondary Outcome Measures: 1. Change from Baseline in Blood Angiotensinogen (AGT) Level [ Time Frame: Parts A, B and E: each up to approximately 12 months; Part D: up to approximately 18 months ]
  • 2. Maximum Observed Plasma Concentration (Cmax) of ALN-AGT01 and of Potential Metabolites [ Time Frame: Parts A, B and E: Up to Day 15; Part D: Up to Day 99 ]
  • 3. Area Under the Concentration-time Curve (AUC) of ALN-AGT01 and of Potential Metabolites [ Time Frame: Parts A, B and E: Up to Day 15; Part D: Up to Day 99 ]

Eligibility Criteria

  • Ages Eligible for Study: 18 to 65 Years (Adult, Older Adult)
  • Sexes Eligible for Study: All
  • Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria:

- Has mild to moderate hypertension with mean sitting systolic blood pressure (SBP) of
>130 and ≤165 mmHg without hypertensive medication for Parts A, B and D, and >135 and
≤165 mmHg without hypertensive medication for Part E

- Parts A and B: Has body mass index (BMI) ≥18 and ≤35 kg/m^2; Part D: Has BMI >35 and
≤50 kg/m^2; Part E: Has BMI ≥18 kg/m^2 and ≤50 kg/m^2

- Has a normal 12-lead electrocardiogram (ECG)

- Is a nonsmoker

Exclusion Criteria:

- Has secondary hypertension

- Has orthostatic hypotension

- Has estimated glomerular filtration rate (eGFR) of <60 mL/min/1.73m^2 - Recently received an investigational agent - Has diabetes mellitus - Has history of any cardiovascular event - Has history of intolerance to SC injection(s)

Contacts and Locations

Contacts

Contact: Alnylam Clinical Trial Information Line 1-877-ALNYLAM clinicaltrials@alnylam.com

Contact: Alnylam Clinical Trial Information Line 1-877-256-9526 clinicaltrials@alnylam.com

Locations

United Kingdom
Clinical Trial Site
Belfast

United Kingdom
Clinical Trial Site
Edinburgh

United Kingdom
Clinical Trial Site
London

United Kingdom
Clinical Trial Site
Manchester

Sponsors and Collaborators

Alnylam Pharmaceuticals

Investigators

Study Director: Medical Director Alnylam Pharmaceuticals

More Information

  • Responsible Party: Alnylam Pharmaceuticals
  • ClinicalTrials.gov Identifier: NCT03934307 History of Changes
  • Other Study ID Numbers: ALN-AGT01-001, 2019-000129-39
  • First Posted: May 1, 2019 Key Record Dates
  • Last Update Posted: June 15, 2021
  • Last Verified: June 2021
  • Individual Participant
    Data (IPD) Sharing
    Statement:

  • Plan to Share IPD: No
  • Studies a U.S. FDA-regulated Drug Product: No
  • Studies a U.S. FDA-regulated Device Product: No
  • Additional relevant MeSH terms: Hypertension